To investigate the effect of cisapride, a selective 5-hydroxytryptamine-4 receptor agonist, on the frequency of nocturnal transient lower oesophageal sphincter relaxations and oesophageal acid exposure in patients with gastro-oesophageal reflux disease.
In a double-blind, placebo-controlled study, 10 patients with gastro-oesophageal reflux disease (six male and four female; mean age, 54 +/- 10.4 years) were randomly assigned to 5-day treatments with cisapride, 10 mg q.d.s., or placebo, separated by a 2-day washout period before the treatment crossover. Sleep stages, lower oesophageal sphincter tone and oesophageal pH were monitored overnight at the end of each treatment regimen. Gastric emptying was assessed before treatment.
Cisapride decreased the frequency of transient lower oesophageal sphincter relaxations during sleep (1.2 +/- 0.2/h vs. 2.7 +/- 0.5/h with placebo; P=0.004) and oesophageal acid exposure (17.2 +/- 9.9% with placebo vs. 7.2 +/- 4.2% with cisapride; P=0.4). Cisapride increased lower oesophageal sphincter tone from 12.7 +/- 2.8 mmHg with placebo to 16.9 +/- 3.9 mmHg (P=0.03), and decreased heartburn episodes and antacid consumption. All patients had normal gastric retention data over 4 h.
In patients with gastro-oesophageal reflux disease, cisapride significantly decreased the frequency of transient lower oesophageal sphincter relaxations during sleep and increased lower oesophageal sphincter pressure without changing gastric emptying. We hypothesize, therefore, that 5-hydroxytryptamine-4 mechanisms are important in the control of transient lower oesophageal sphincter relaxations in humans.